CN113559318B - Chiral conductive repair scaffold for promoting nerve function recovery and preparation method thereof - Google Patents

Chiral conductive repair scaffold for promoting nerve function recovery and preparation method thereof Download PDF

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CN113559318B
CN113559318B CN202110757555.0A CN202110757555A CN113559318B CN 113559318 B CN113559318 B CN 113559318B CN 202110757555 A CN202110757555 A CN 202110757555A CN 113559318 B CN113559318 B CN 113559318B
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nerve
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CN113559318A (en
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黄忠兵
李娅
李小慧
尹光福
蒲曦鸣
廖晓明
王娟
方欣雨
吴玉
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Sichuan University
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Abstract

The invention discloses a preparation method of a chiral conductive repair scaffold for promoting nerve function recovery. Firstly, coating a polypyrrole nanoparticle conductive layer on a self-made polylactic acid electrostatic spinning fiber membrane by an electrochemical deposition method, and rolling the polypyrrole nanoparticle conductive layer into a tube; and then adding self-made self-assembled chiral fiber hydrogel into the tube, and obtaining the chiral fiber hydrogel composite conductive scaffold through electrostatic attraction and hydrogen bond action. The chiral conductive scaffold can not only induce the repair of peripheral nerve injury, but also promote the functional recovery of the repaired nerve. The preparation process is simple, the processing conditions are mild, the operation and the control are easy, the obtained stent has good biocompatibility, surface optical activity, conductivity and biodegradability, the mechanical property of the stent is matched with nerve tissues, the stimulation of damaged tissue electrical signals and matrix optical activity dual signals can be provided, and the stent has potential clinical application value in the field of peripheral nerve repair.

Description

Chiral conductive repair scaffold for promoting nerve function recovery and preparation method thereof
Technical Field
The invention relates to the technical field of tissue engineering materials, in particular to a chiral conductive repair scaffold with the function of promoting recovery of nerve function and a preparation method thereof.
Background
Traditional pharmacotherapy of peripheral nerve injury and traditional epineurial suturing have limited efficacy, and autologous nerve transplantation remains the gold standard for treating peripheral nerve injury that cannot be directly sutured. However, autologous nerve transplantation has the defects of limited donor source, donor area function loss, donor size mismatching and the like, and is difficult to popularize in a large clinical scale. For peripheral nerve injury, an ideal nerve conduit needs to be designed and prepared, and the nerve conduit is connected to the broken ends of two sides of a nerve defect in a sewing mode. The nerve conduit also needs to combine physical or chemical signals to directionally regulate and control the behaviors of nerve cells and nerve axons, so that the degeneration and degeneration of injured nerve stumps are delayed, the proliferation, the ordered arrangement and the myelination of Schwann cells in the nerve conduit are promoted, and the growth of proximal nerve axons is promoted; and through a proper repair microenvironment, the growing nerve axons can extend to the far end, so that the damaged nerves can be regenerated, and the functional dominance of the nerves on the damaged far-end connected target organs can be restored. However, compared with the autologous nerve graft, the regenerated nerve fibers in the artificial nerve conduit are fewer and thinner, and the functional recovery of the innervated target organ is generally less than 30%.
The existing research shows that electrical stimulation is implemented through the conductive polymer scaffold material, so that Schwann cells can be promoted to be orderly arranged and grow, the expression of nerve factor protein and the directional growth of nerve axons can be promoted, and the repair of nerve injured tissues can be promoted. Polypyrrole is a conductive functional polymer material which can be used for preparing tissue engineering scaffolds and has good biocompatibility; the camphorsulfonic acid is a chiral molecule with good in vivo histocompatibility, and chiral carbon of the camphorsulfonic acid can be induced to be combined with the same side of hetero atoms on a conductive polymer chain through the action of hydrogen bonds, so that the polymer chain forms a spiral structure. The polypyrrole nano-particles doped with acid radicals are coated and combined with a biodegradable flexible polylactic acid electrospinning film to form a polypyrrole nano-particle coated composite silk film with certain strength and conductivity, so that the polypyrrole nano-particle coated composite silk film can be used for repairing peripheral nerves; and the growth of the nerve axon and the regeneration of the nerve injury can be promoted by the electrical stimulation of the composite material.
In living bodies and tissues, a plurality of chiral molecules are self-assembled to form a biological structure with special three-dimensional conformation and function, and are further assembled to form organelles and extracellular matrixes with three-dimensional chiral structures, so that macroscopic asymmetric forms of higher living bodies such as tissues and organs are formed, and corresponding functions of the tissues and the organs are further performed. Therefore, chiral structure is considered as one of the key factors for the formation of living tissue.
The chiral nanofiber hydrogel has intelligent responsiveness to external stimulation due to the self-assembly characteristic, and can provide a dynamic microenvironment for cell growth; the size of the formed three-dimensional nanofiber chiral structure is close to the size of natural collagen in a human body, and the three-dimensional nanofiber chiral structure has unique advantages in the aspect of constructing a cell culture scaffold material. In addition, the hydrogel fibers have the characteristics of good biocompatibility, mechanical property, chiral structure and the like, controllability and designability, and can be used for controllably adjusting various behaviors (such as adhesion, proliferation, growth and the like) of cells according to needs. Therefore, these hydrogel fibers have been the focus of research in recent years as a new class of soft materials.
The 1, 4-phthalic acid amide-phenylalanine derivative has a molecular chiral structure which is arranged in a spatially asymmetric way, can be self-assembled into a supermolecular spiral nanofiber with the same optical activity, and has proved that the optical activity of the chiral fiber hydrogel has a significant influence on the cell behaviors of various cells. For example, in the field of inducing stem cell differentiation, the levorotatory nanofiber hydrogel matrix can significantly enhance the osteogenic capacity of bone marrow mesenchymal cells, while the dextrorotatory nanofiber hydrogel matrix significantly enhances the adipogenic capacity of bone marrow mesenchymal cells (Wei Yan et al, Advanced Materials,2019,31, 1900582); in Retinal Progenitor Cell (RPC) differentiation, the helical orientation of the chiral nanofibers can effectively regulate RPC differentiation, with right-handed nanofibers significantly promoting RPC differentiation into neurons, and left-handed nanofibers reducing this differentiation (Sun Na et al, Bioactive Materials,2021,6, 990-.
In the application, 1, 4-phthalic acid amide-phenylalanine chiral fiber hydrogel is combined on the surface of a polypyrrole-polylactic acid conducting film doped with dodecylbenzene sulfonic acid (or D-camphorsulfonic acid or L-camphorsulfonic acid), so that the polypyrrole-polylactic acid conducting film has good biocompatibility, optical activity, conductivity, biodegradability and mechanical matching property, and can provide electrical signals and matrix optical activity dual-signal stimulation for regenerated nerve tissues. The composite material is suitable for manufacturing the chiral hydrogel composite conductive nerve scaffold for repairing the long-distance peripheral nerve defect.
The existing composite conductive nerve scaffold is mostly invented for enhancing the conductivity or biocompatibility, or compounded with various conductive materials, growth factor components and the like (CN202010181686.4, CN201910783534.9, CN201810117839.1, CN201610549724.0, CN201610806967.8, CN201410478759.0, CN201210280734.0 and CN2011100) 54237.4); also in parallel structure, pore channel structure or cross-linked network structure (CN202010180359.7, CN201810058190.0, CN201610260848.7) for enhancing nerve cell growth guiding or blood vessel regeneration capacity, and single type or composite type (CN201910459198.2, CN201610118825.2) in three-dimensional bionic design (CN201710488463.0, CN201610327773.X) for directly introducing biological structure and components for improving comprehensive performance. The existing chiral hydrogel is mainly focused on three-dimensional cell culture systems (CN202010420945.4 and CN201811085214.8) as extracellular matrix and cell scaffold materials (CN202010323061.7, CN201910590861.2 and CN201310658697.7) for promoting cell differentiation in nerve tissue repair. The invention of the conductive scaffold combined with the artificially synthesized chiral hydrogel material is not disclosed. The invention combines the optical activity of the substrate of the chiral supramolecular hydrogel disclosed in CN202010323061.7 and the dual-signal stimulation of the electric signal of the chiral camphor sulfonic acid doped polypyrrole-polylactic acid conductive nerve scaffold to prepare the chiral hydrogel composite conductive nerve scaffold for long-distance nerve defect repair.
Disclosure of Invention
The purpose of the research is to compound 1, 4-benzene dicarboxylic acid amide-phenylalanine chiral fiber hydrogel on a polypyrrole-polylactic acid film doped with dodecylbenzene sulfonic acid (or D-or L-camphorsulfonic acid) so as to provide electric stimulation and matrix optical rotation dual-signal stimulation, so that the chiral hydrogel composite conductive nerve scaffold which has good biocompatibility, optical rotation, conductivity and biodegradability, has mechanical properties matched with nerve tissues, can provide electric stimulation and matrix optical rotation dual-signal stimulation and is suitable for long-distance peripheral nerve defect repair is obtained. In order to achieve the aim, the invention provides a chiral conductive repair scaffold for promoting the recovery of nerve functions and a technical scheme of a preparation method thereof.
On one hand, the invention provides a chiral conductive repair scaffold for promoting the recovery of nerve function, which is prepared by taking D-type or L-type 1, 4-benzene dicarboxylic acid amide-phenylalanine chiral molecules, polylactic acid electrospun membranes, pyrrole monomers and dodecyl benzene sulfonic acid or chiral camphor sulfonic acid as raw materials through electrochemical deposition reaction, self-assembly of chiral fibers and hydrogen bond combination; the inner layer of the chiral conductive repair scaffold material is a polylactic acid electrospun membrane coated by dodecylbenzene sulfonic acid or chiral camphor sulfonic acid doped polypyrrole nano particles, and the polylactic acid electrospun membrane has conductivity; the outer layer of the chiral conductive repairing scaffold material is D-type or L-type chiral gel fiber formed by self-assembly of D-type or L-type 1, 4-phthalic acid amide-phenylalanine chiral molecules, and the chiral gel fiber has good hydrophilicity and an optical chiral structure. After the chiral conductive repair stent is sutured at a peripheral nerve injury part through an operation, the nerve axon regeneration repair and the function recovery of the dominated target muscle can be stimulated by double signals through the electric signals and the chiral signals on the surface of the stent, so that the repair stent has the function of promoting the nerve function recovery by the cooperation of chirality and electric stimulation.
On the other hand, the preparation method of the chiral conductive repairing scaffold for promoting the recovery of the nerve function comprises the following steps: a) preparing polylactic acid electrospun membrane: the polylactic acid spinning solution is added at the ratio of 0.8-1.5 multiplied by 10 5 Spinning for 20-60 minutes under the electrostatic field of V/m, collecting and drying on the indium tin oxide-plated polyester conductive film to obtain a polylactic acid fiber film A; b) preparing an electrochemical deposition solution: adding 2-20 mM of sodium dodecyl benzene sulfonate (or chiral camphor sulfonic acid) and 10-400 mM of pyrrole into ultrapure water in sequence to prepare an electrodeposition liquid B; c) preparing a polypyrrole conductive film by electrochemical deposition: taking an electrospun membrane A with an indium tin oxide-plated polyester conductive film as a carrier as an anode and a platinum sheet as a cathode, immersing the electrospun membrane A into a deposition solution B, applying a direct current of 8-12 mA/cm between the two electrodes, performing electrodeposition for 10-30 min, cleaning and drying to obtain the electrospun membrane A with the size of (2-30) × (6-30) cm 2 The polypyrrole-polylactic acid composite film C; d) preparing a 1, 4-phthalic acid amide-phenylalanine chiral solution: dispersing D/L type 1, 4-phthalic acid amide-phenylalanine chiral molecules in ultrapure water, and heating to 60-100 ℃ until the D/L type 1, 4-phthalic acid amide-phenylalanine chiral molecules are completely dissolved to prepare 0.01-10mg/mL D/L-1, 4-phthalic acid amide-phenylalanine chiral fiber hydrogel F; e) preparing a chiral fiber hydrogel compounded polypyrrole-polylactic acid conductive nerve scaffold: rolling the composite membrane C into a circular tube E with the diameter of 0.5-5 mm and the length of 2-8 mm, and injecting D/L-1, 4-phthalic acid amide-phenylalanine chiral fiber hydrogel F into the tube; thereby obtaining the final product of the chiral fiber hydrogel composite polypyrrole-polylactic acid conductive nerve scaffold.
As a further aspect of the present invention, in step a), the parameters of electrospinning: the voltage is 1.0 to 1.5 x 10 5 V/m, the spinning time is 20-60 minutes, and the electric spinning receiving plate adopts an indium tin oxide polyester conductive film A.
In a further embodiment of the present invention, in step b), the concentration of dodecylbenzenesulfonic acid (or D-or L-camphorsulfonic acid) is 2 to 20mM, and the concentration of pyrrole monomer is 10 to 400 mM.
As a further aspect of the present invention, in step c), the electrochemical deposition method: the polylactic acid electrospun membrane A with the indium tin oxide-plated polyester conductive membrane as a carrier is used as an anode, a platinum sheet is used as a cathode, the current of electrodeposition is 8-12 mA/cm, and the time of electrodeposition is 10-30 min.
As a further scheme of the invention, in the step D), the dispersion temperature of the D/L type 1, 4-phthalic acid amide-phenylalanine chiral molecule in the ultrapure water is 60-100 ℃, and the concentration after dispersion is 0.01-10 mg/mL.
As a further scheme of the invention, in the step e), the diameter of a round pipe made of the polypyrrole-polylactic acid composite film C doped with dodecylbenzene sulfonic acid (or D-type or L-type camphor sulfonic acid) is 0.5-5 mm, and the length of the round pipe is 2-8 mm; the volume of the D-type or L-type chiral fiber hydrogel F injected into the round tube is 0.2-5 mL.
The polypyrrole-polylactic acid conductive nerve scaffold compounded by the 1, 4-phthalic acid amide-phenylalanine chiral fiber hydrogel can be prepared by the preparation method.
Compared with the prior art, the invention has the beneficial effects that:
the polypyrrole-polylactic acid conductive nerve scaffold compounded by the 1, 4-phthalic acid amide-phenylalanine chiral fiber hydrogel prepared by the method has good biocompatibility, optical rotation, conductivity, biodegradability and mechanical matching, and can be used for electrical stimulation and matrix optical rotation dual-signal stimulation therapy for long-distance peripheral nerve defect repair. The method has the advantages of simple process, mild reaction conditions, easy operation and potential application value in the field of peripheral nerve repair.
Drawings
FIG. 1 is a schematic diagram of a process for preparing a surface chiral fiber hydrogel conductive composite material.
Fig. 2 is a scanning electron microscope photograph of the chiral fiber hydrogel compounded polypyrrole-polylactic acid conductive nerve scaffold material.
Fig. 3 is an atomic force microscope photograph of the chiral fiber hydrogel compounded polypyrrole-polylactic acid conductive nerve scaffold.
FIG. 4 is a statistical chart of the conductivity of the conductive composite film before and after electrostatic assembly of two chiral fibers; denotes p <0.05 between the relevant two groups.
FIG. 5 is a living cell staining picture of Schwann cells growing for 5 days on a polypyrrole-polylactic acid conductive nerve scaffold material compounded by two different chiral fiber hydrogels. Obviously, on the right handmade fiber composite surface, a large number of schwann cells exist; and only a few Schwann cells grow on the composite surface of the left-handed chiral fiber.
FIG. 6 is a statistical plot of the growth activity (MTT) of Schwann cells on a polypyrrole-polylactic acid conductive nerve scaffold material compounded by two different chiral fiber hydrogels; indicates p <0.05 between the relevant groups.
FIG. 7 is a comparison graph of the compound electromyographic potential recovery rate of the polypyrrole-polylactic acid guide nerve scaffold material compounded by different chiral fibers and hydrogels after the injury of the sciatic nerve of a rat is repaired.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
Dissolving polylactic acid in hexafluoroisopropanol to prepare spinning solution with the mass volume fraction of 4 wt%; mixing polylactic acid spinning solution at 0.9X 10 5 Spinning for 60 minutes under the electrostatic field of V/m, preparing a nanofiber film on the indium tin oxide-plated polyester conductive film, anddrying in a vacuum drying oven at normal temperature to obtain the polylactic acid fiber membrane A. Sodium dodecylbenzenesulfonate and pyrrole were added to ultrapure water to prepare electrodeposition liquid B at concentrations of 7mM and 100mM, respectively. And taking the fiber membrane A with the indium tin oxide-plated polyester conductive film as a carrier as an anode, taking a platinum sheet as a cathode, immersing the fiber membrane A into the deposition solution C, applying direct current of 10mA/cm between the two electrodes, electrodepositing for 20min, and cleaning and drying to obtain the polypyrrole-polylactic acid composite membrane C. Ultrasonically dispersing D-type 1, 4-phthalic acid amide-phenylalanine chiral molecules in ultrapure water to prepare 0.1mg/mL 1, 4-phthalic acid amide-phenylalanine dextrorotatory chiral solution. Respectively adding 200 mu L/cm of the composite film C on the circular tube E 2 The chiral solution F is subjected to hydrogen bond combination for 30min and then dried in a vacuum drying oven at 36 ℃, and the final product, namely the polypyrrole-polylactic acid conductive nerve scaffold compounded by the 1, 4-phthalic acid amide-phenylalanine chiral fiber hydrogel is obtained.
Example 2
Dissolving polylactic acid in hexafluoroisopropanol to prepare spinning solution with mass volume fraction of 7.5 wt%; mixing polylactic acid spinning solution at 1.5X 10 5 Spinning for 20 minutes under a V/m electrostatic field, preparing a nanofiber membrane on the indium tin oxide-plated polyester conductive film, and drying at normal temperature in a vacuum drying oven to obtain the polylactic acid fiber membrane A. In ultrapure water, D-type camphorsulfonic acid) and pyrrole were added to prepare respective concentrations of 12mM and 200mM, to obtain electrodeposition liquid B. And taking the fiber film A with the indium tin oxide-plated polyester conductive film as a carrier as an anode and a platinum sheet as a cathode, immersing the fiber film A into the deposition solution C, applying direct current of 12mA/cm between the two electrodes, electrodepositing for 10min, and cleaning and drying to obtain the polypyrrole-polylactic acid composite film C. Ultrasonically dispersing D-type 1, 4-phthalic acid amide-phenylalanine chiral molecules in ultrapure water to prepare 0.25mg/mL 1, 4-phthalic acid amide-phenylalanine dextrorotatory chiral solution. Respectively adding 100 mu L/cm of the composite film C on the circular tube E 2 The chiral solution F is subjected to hydrogen bond combination for 25min and then dried in a vacuum drying oven at 36 ℃, and the final product, namely the polypyrrole-polylactic acid conductive nerve scaffold compounded by the 1, 4-phthalic acid amide-phenylalanine chiral fiber hydrogel is obtained.
Embodiment 3
Dissolving polylactic acid in hexafluoroisopropanol to prepare spinning solution with the mass volume fraction of 11 wt%; mixing polylactic acid spinning solution at 1.2X 10 5 Spinning for 45 minutes under the electrostatic field of V/m, preparing a nanofiber membrane on the indium tin oxide plated polyester conductive film, and drying at normal temperature in a vacuum drying oven to obtain the polylactic acid fiber membrane A. L-type camphorsulfonic acid and pyrrole were added to ultrapure water to prepare respective concentrations of 20mM and 80mM, thereby obtaining a bath B. And taking the fiber membrane A with the indium tin oxide-plated polyester conductive film as a carrier as an anode, taking a platinum sheet as a cathode, immersing the fiber membrane A into the deposition solution C, applying a direct current of 8mA/cm between the two electrodes, electrodepositing for 30min, and cleaning and drying to obtain the polypyrrole-polylactic acid composite membrane C. Ultrasonically dispersing D-type 1, 4-phthalic acid amide-phenylalanine chiral molecules in ultrapure water to prepare 1.2mg/mL 1, 4-phthalic acid amide-phenylalanine dextrorotatory chiral solution. Respectively adding 80 mu L/cm of the composite film C on the circular tube E 2 The chiral solution F is subjected to hydrogen bond combination for 20min and then dried in a vacuum drying oven at 37 ℃, so that the final product, namely the polypyrrole-polylactic acid conductive nerve scaffold compounded by the 1, 4-phthalic acid amide-phenylalanine chiral fiber hydrogel is obtained.
FIG. 1 is a schematic diagram of a process for preparing a surface chiral fiber hydrogel conductive composite material.
Fig. 2 is a scanning electron microscope photograph of the chiral fiber hydrogel compounded polypyrrole-polylactic acid conductive nerve scaffold material. In FIG. 2a, a fibrous chiral gel (shown by white arrows) coated on the material, about 50nm in diameter, with a distinct fibrous structure, and multiple fibers spiraling side-by-side to form a larger diameter, more distinct, stranded helical structure, can be clearly observed; more voids were formed between them and polypyrrole nanoparticles (shown by black arrows) exposed between the voids of the gel fibers were also seen. In fig. 2b, the chiral gel fiber coated on the surface of the conductive composite film on the right-handed coating material (shown by red arrow) can be observed more clearly, the diameter of the chiral gel fiber is about 50nm, the fiber is spread to form a film with small gaps, and the polypyrrole nanoparticles (shown by black arrow) exposed in the gaps of the chiral gel fiber can be also seen.
Fig. 3 is an atomic force microscope photograph of the chiral fiber hydrogel compounded polypyrrole-polylactic acid conductive nerve scaffold. The left-handed helical structure of the gel fibers (as indicated by the arrows and the chiral directions in the above schematic diagram) can be more clearly observed in FIG. 3a, and it is shown that the left-handed chiral gel fibers are mostly arranged in a single dispersion, and the fiber diameter is about 40 nm; while the right-handed chiral gel fiber in FIG. 3b shows a plurality of strands twisted together, the twisted helical structure (shown by the arrows and the chiral direction in the above schematic diagram) of the gel fiber can be observed more clearly, and the diameter of the twisted helical structure is about 40-90 nm.
FIG. 4 is a statistical chart of the conductivity of the conductive composite film before and after electrostatic assembly of two chiral fibers; indicates p <0.05 between the relevant groups. Fig. 4 clearly shows that, after two chiral fibers are electrostatically assembled on the polypyrrole conductive material, the conductivity of the material is significantly reduced, but the conductivity of the material still maintains 8.1S/cm, and the material can transmit good electric signals in cells and in vivo nerve repair.
FIG. 5 is a living cell staining picture of Schwann cells growing for 5 days on a polypyrrole-polylactic acid conductive nerve scaffold material compounded by two different chiral fiber hydrogels. As can be seen from fig. 5, on the right handmade fiber composite surface, there are a large number of schwann cells; and only a few Schwann cells grow on the composite surface of the left-handed chiral fiber.
FIG. 6 is a statistical plot of the growth activity (MTT) of Schwann cells on a polypyrrole-polylactic acid conductive nerve scaffold material compounded by two different chiral fiber hydrogels; indicates p <0.05 between the relevant groups. As can be seen from fig. 6, the number of schwann cells growing on the composite surface of the dextrorotatory chiral fibers is significantly greater than that on the composite surface of the levorotatory chiral fibers in the culture time of 1, 3 and 5 days, which indicates that the dextrorotatory chiral fibers can significantly promote the growth of schwann cells on the surface of the chiral conductive material and the expression of the neuro-related protein, and this may result from the better hydrophilic property of the dextrorotatory chiral surface.
FIG. 7 is a comparison graph of the compound electromyographic potential recovery rate of the polypyrrole-polylactic acid tutor nerve scaffold material compounded by different chiral fibers in sleep after the rat sciatic nerve injury is repaired. As can be seen from FIG. 7, different prepared chiral fiber hydrogel composite conductive catheter stents were sutured at 1cm injury of rat sciatic nerve; the recovery rate of the composite electromyography potential of the dextro-fiber composite scaffold is the highest at 4, 8 and 12 weeks after operation, which indicates that the dextro-fiber hydrogel composite conductive scaffold has the best recovery of the regenerative nerve function.
The present invention is not limited to the details of the above-described exemplary embodiments, and may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The embodiments are exemplary and non-limiting, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein. Furthermore, it should be understood that although the present specification describes embodiments, not every embodiment includes only a single embodiment, and such description is for clarity purposes only, and it is to be understood that all embodiments may be combined as appropriate by one of ordinary skill in the art to form other embodiments as will be apparent to those of skill in the art from the description herein.

Claims (3)

1. A chiral conductive restoration scaffold for promoting nerve function restoration is characterized in that the scaffold is a polypyrrole conductive composite nerve restoration scaffold with a surface chiral structure, and is prepared by taking a D-type or L-type 1, 4-phthalic acid amide-phenylalanine chiral molecule, a polylactic acid electrospun membrane, a pyrrole monomer and D-type or L-type camphorsulfonic acid as raw materials through electrochemical deposition reaction, self-assembly of chiral fibers and hydrogen bond combination; the inner layer of the chiral conductive repair scaffold material is a polylactic acid electrospun membrane coated by the D-type or L-type camphorsulfonic acid doped polypyrrole nano particles, and has conductivity and doped small molecule chirality; the outer layer of the chiral conductive repairing scaffold material is D-type or L-type chiral fiber hydrogel formed by self-assembly of D-type or L-type 1, 4-phthalic acid amide-phenylalanine chiral molecules, and has a hydrophilic and chiral spiral structure; the corresponding chiral fiber hydrogel is identified by chiral camphorsulfonic acid and is self-assembled and combined between the conductive inner-layer silk film and the outer-layer chiral fiber hydrogel film;
the D-type camphorsulfonic acid doped conductive composite silk membrane is combined with the D-type chiral fiber hydrogel, and the L-type camphorsulfonic acid doped conductive composite silk membrane is combined with the L-type chiral fiber hydrogel.
2. The preparation method of the chiral conductive repair scaffold for promoting the recovery of nerve function according to claim 1, which is characterized by comprising the following steps:
a) preparing a polylactic acid nano electrospun film A on the polyester conductive film; the electrostatic spinning parameters are as follows: the spinning voltage is 0.8-1.5 multiplied by 10 5 V/m, the spinning time is 20-60 minutes, and the receiving sheet of the electrospinning film is plated with an indium tin oxide polyester conductive film;
b) respectively adding D-type or L-type camphorsulfonic acid and pyrrole monomers into ultrapure water, wherein the concentrations of the D-type or L-type camphorsulfonic acid and pyrrole monomers are respectively prepared into 2-20 mM and 10-400 mM to be used as electrochemical deposition liquid B;
c) immersing a polylactic acid electrospun membrane A taking a polyester conductive film as a carrier as an anode and a platinum sheet as a cathode into an electrodeposition liquid B, applying a direct current of 8-12 mA/cm between the two electrodes, performing electrodeposition, oxidation and polymerization for 10-30 min, cleaning and drying to obtain a polylactic acid electrospun membrane A with the size of (2-30) × (6-30) cm 2 The D-type or L-type camphor sulfonic acid doped polypyrrole-polylactic acid conductive composite silk membrane C;
d) dispersing 0.01-10mg/mL D-type or L-type 1, 4-phthalic acid amide-phenylalanine chiral molecules in ultrapure water, heating to 60-100 ℃ to completely dissolve the D-type or L-type 1, 4-phthalic acid amide-phenylalanine chiral molecules, and slowly self-assembling the D-type or L-type 1, 4-phthalic acid amide-phenylalanine chiral fiber hydrogel for 20-50 min to obtain D-type or L-type 1, 4-phthalic acid amide-phenylalanine chiral fiber hydrogel F;
e) rolling the D-type or L-type camphorsulfonic acid doped conductive composite silk film C into a circular tube E with the diameter of 0.5-5 mm and the length of 2-8 mm, and uniformly injecting D-type or L-type chiral fiber hydrogel F into the tube; after 5.0-60 min of polar bond assembly and combination, obtaining a final product, namely a chiral fiber hydrogel composite camphorsulfonic acid doped polypyrrole conductive restoration scaffold; the conductive composite silk film round tube doped with the D-type camphorsulfonic acid is combined with the D-type chiral fiber hydrogel, and the conductive composite silk film round tube doped with the L-type camphorsulfonic acid is combined with the L-type chiral fiber hydrogel.
3. The preparation method of the chiral conductive restoration scaffold for promoting the recovery of nerve functions as claimed in claim 2, wherein in the step E), the length of the round tube E made of the D-type or L-type camphor sulfonic acid doped polypyrrole-polylactic acid composite membrane is 6-8 mm; the volume of the D-type or L-type chiral fiber hydrogel F injected into the round tube is 3-230 mL.
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